Effect of nutrition‐based prehabilitation on the postoperative outcomes of patients with esophagogastric cancer undergoing surgery: A systematic review and meta‐analysis

Abstract Background Meta‐analyses have primarily focused on the effects of exercise‐based prehabilitation on postoperative outcomes and ignored the role of nutritional intervention. In this study, we filled this gap by investigating the effect of nutrition‐based prehabilitation on the postoperative outcomes of patients who underwent esophagectomy and gastrectomy. Methods Five electronic databases, namely, PubMed, the Web of Science, Embase, Cochrane Library, and CINAHL, were searched. Adults diagnosed with esophagogastric cancer who were scheduled to undergo surgery and had undergone uni‐ or multimodal prehabilitation, with at least a week of mandatory nutritional intervention, were included. Forest plots were used to extract and visualize the data from the included studies. The occurrence of any postoperative complication was considered the primary endpoint. Results Eight studies met the eligibility criteria, with five randomized controlled trials (RCTs) and three cohort studies. In total, 661 patients were included. Any prehabilitation, that is, unimodal (only nutrition) and multimodal prehabilitation, collectively decreased the risk of any postoperative complication by 23% (95% confidence interval [CI] = 0.66–0.90). A similar effect was exclusively observed for multimodal prehabilitation (risk ratio [RR] = 0.78, 95% CI = 0.66–0.93); however, it was not significant for unimodal prehabilitation. Any prehabilitation significantly decreased the length of hospital stay (LOS) (weighted mean difference = −0.77, 95% CI = −1.46 to −0.09). Conclusions Nutrition‐based prehabilitation, particularly multimodal prehabilitation, confers protective effects against postoperative complications after esophagectomy and gastrectomy. Our findings suggest that prehabilitation slightly decreases LOS; however, the finding is not clinically significant. Therefore, additional rigorous RCTs are warranted for further substantiation.

In 2020, 604,100 and 1,089,103 new cases of esophageal cancer (EC) and gastric cancer (GC), respectively, were reported worldwide; this accounts for 3.1% and 5.6% of all cancers.Furthermore, 1,312,869 patients (13.2%) with these two upper gastrointestinal tract (UGI) tumors died in 2020. 1 Gastrointestinal (GI) tumors exhibit the unique characteristic of being tumors in the primary system of food intake and digestion.These conditions and iatrogenic intervention can exert several adverse effects on the nutrition absorption of patients.Esophagogastric resection is not only a curative-intent therapy, but also the mainstay of treatment. 2However, it is frequently accompanied by poor postoperative outcomes such as pulmonary complications, anastomotic leak, longer length of hospital stay (LOS), and increased mortality rate. 3,4o optimize the perioperative procedure, enhanced recovery after surgery (ERAS), a broadly accepted perioperative multidisciplinary care procedure, has been developed and proven to help accomplish earlier hospital discharge without hampering postoperative care for esophagectomy and gastrectomy. 5,6Although, data are inadequate to draw solid conclusions, the ERAS society has still given a moderate recommendation grade for prehabilitation for esophagectomy and major abdominal surgery. 7Surgical prehabilitation occurs between the time of cancer diagnosis and the start of surgical treatment; it includes nutritional support such as oral nutritional supplement (ONS) and diet counseling, exercise support such as aerobic and resistance exercise, and psychological support such as anxiety attenuation to optimize the preoperative functional capacity. 8,9In patients receiving GI surgery, the risk of malnutrition is present both pre and postoperatively. 10erioperative malnutrition frequently indicates higher LOS postoperatively, morbidity, mortality, and medical costs. 11,12This makes nutritional prehabilitation a vital measure to prepare or optimize patients for surgery, and not necessarily to replace nutritional deficits. 13ost meta-analyses [14][15][16][17] have only focused on studies on exercise prehabilitation, with the effects on short-and long-term postoperative outcomes being inconsistent.In one meta-analysis, 18 researchers investigated the effect of multimodal prehabilitation on the postoperative outcomes of patients who underwent hepatobiliary, colorectal, and UGI cancer surgery; however, they only included three studies on UGI cancer, thereby providing less persuading evidence.Nevertheless, in a systematic review and meta-analysis, Gillis et al. 19 have reported promising results: after colorectal surgery, only nutritional prehabilitation or combination with an exercise program decreased hospital stay by 2 days.
Therefore, in the present systematic review and metaanalysis, we investigated the effects of unimodal or multimodal prehabilitation, with mandatory nutrition prehabilitation, on the clinical outcomes of patients with esophagogastric cancer who were awaiting surgery.The primary objective was to observe the changes in postoperative complications.The secondary objective was to assess the changes in LOS, readmission, and mortality.

| METHODS
The reporting guidance of The Preferred Reporting Items for Systematic Reviews and Meta-Analyses was followed for this systematic review and meta-analysis. 20The review protocol was recorded and registered in PROSPERO (registration number: CRD42022314766).

| Objective
The primary objective of this meta-analysis was to investigate the effect of nutritional prehabilitation with or without exercise and/or psychological support on the postoperative complications of patients with gastroesophageal cancer undergoing surgery.Our second objective was to determine whether prehabilitation can decrease LOS, readmission, and mortality compared with patients who received conventional care.

| Search strategy
Five electronic databases, namely, PubMed, the Web of Science, Embase, Cochrane Library, and CINAHL, were searched.Without restrictions on countries or study types, all English publications until June 1, 2023, were searched.Furthermore, the references of all the selected studies and associated reviews were independently screened to identify additional studies that were omitted in the original search.The search strategy was established based on enhanced recovery after surgery, esophagogastric cancer, meta-analysis, prehabilitation, preoperative exercise, preoperative nutrition "P" (patients with EC and/or GC) and "I" (prehabilitation, i.e., preoperative nutrition with or without exercise and/or psychological support) in the PICOS principle (Appendix S1).

| Study selection
After performing the initial search and removing duplicates, two reviewers (YHW and QYG) independently assessed the titles and abstracts of full-text reviews.All disagreements were resolved by a third author (ZZC).All eligible studies, including references from the selected studies and reviews, were included.Adults (more than 18 years of age) with esophagogastric cancer who were planning to undergo surgery were included.Studies with multiple cancer types that were not separately analyzed were excluded.Nutritional prehabilitation, defined as the preoperative application of ONS or enteral nutrition (EN) with or without dietary advice for at least 7 days, thereby altering macronutrient (carbohydrate, protein, and fat) intake, was mandatory.Exercise prehabilitation included preoperative aerobic exercises, strength or resistance exercises, and inspiratory muscle training at the hospital or home.Psychological prehabilitation included preoperative consultation, motivational interviewing, and psychometric screening.Only studies that included nutritional prehabilitation were considered.Unimodal prehabilitation only included nutrition, whereas, multimodal included two or three interventions, with nutrition being one intervention.In terms of nutritional prehabilitation, the patients in the control group were not subjected to any intervention (routine daily diet as a negative control) or subjected to only nutritional counseling.However, some high-risk patients (<50% in the control group) were allowed to undergo the same interventions performed in the prehabilitation group.Preoperative exercise and psychological interventions were both negative controls in the control group.Furthermore, postoperative patient management was similar in both groups, for example, both underwent the ERAS program.Only original randomized controlled trials (RCTs) and cohort studies were included.

| Data extraction
The data were independently extracted by two reviewers (YHW and QYG).Any disagreements were resolved by a third reviewer (ZZC).The data extraction sheet was assessed on two studies that were randomly selected.If available, the following data were extracted: (1) baseline characteristics, (2) intervention characteristics, and (3) reported outcomes.The corresponding author was contacted to address missing data.Data management and extraction were performed using Zotero 6.0.26 (Corporation for Digital Scholarship, USA) and Excel version 2305 (Microsoft, USA).

| Quality assessment
The risk of bias in RCTs was assessed using the Cochrane Collaboration's tool, with six domains.Bias was graded as high, low, or unclear risk. 21The assessment was completed using Review Manager (RevMan) 5.4.1 (Cochrane, UK).The Newcastle-Ottawa Scale (NOS) was used to assess the cohort studies.A star system (a maximum of 9 stars) was used to judge the detection of selection, comparability, and exposure or outcome. 22Higher stars indicate a lower risk of bias.Two reviewers (YHW and QYG) conducted the assessment.Any disagreements were resolved by a third reviewer (ZZC).

| Statistical analysis
Forest plots were generated to investigate the effects of prehabilitation on postoperative outcomes.Pooled risk ratio (RR) was used for categorical data, standard mean difference for varying units, and weighted mean difference (WMD) for continuous variables, with a 95% confidence interval (CI).The I 2 test was used to assess heterogeneity.If I 2 < 50% or p > 0.1, a fixed-effects model was applied, otherwise, a random-effects model was applied.Subgroup analysis was stratified by intervention, cancer type, surgical care, and research design.If specific studies only provided median and interquartile range, the mean and standard deviation (SD) were estimated. 23,24If more than 10 studies were included, the Egger test was used to assess publication bias. 25RevMan 5.4.1 (Cochrane, UK) was used to perform data analysis.A p < 0.05 indicated statistical significance.

| Search outcomes
After screening the five online databases based on the predeveloped search strategy, 717 studies were identified: 132 in PubMed, 278 in the Web of Science, 201 in Embase, 54 in Cochrane Library, and 52 in CINAHL.After removing duplicate studies and studies whose titles or abstracts did not meet the inclusion criteria and adding eight possibly qualified studies from the references, 52 studies were included for full-text review.In total, eight studies [26][27][28][29][30][31][32][33] (five RCTs and three cohort studies) met the inclusion criteria and were included in the final analysis via additional screening (Figure 1).

| Baseline characteristics
Eight studies from five countries between 2015 and 2022 were analyzed (Table 1).1,33 Halliday et al. 33 used propensity scores to match the prehabilitation and control groups; however, no significant differences were observed in the demographic factors, except for respiratory comorbidity before matching.Therefore, we adopted the data of the unmatched groups in the subsequent analysis. In total 661 operative patients were included, with 351 in the prehabilitation group and 310 in the control group. Th mean or median age range was 60.5-68, except for the study conducted by Wang et al. 30 who did not calculate the mean or median age.More than 50% of the patients were diagnosed with esophageal and esophagogastric junction cancer (58%, 385/661); in contrast, the remaining patients were diagnosed with GC (42%, 276/661).Furthermore, 56%-100% of patients in the selected studies received at least one type of neoadjuvant therapy; however, two studies 29,30 did not provide any information on neoadjuvant therapy.Five studies 26,27,29,32,33 were conducted under the ERAS setting, comprising immediate feeding, early mobilization, and early drain and tube removal postoperatively, 34 in the intervention and control groups.

| Intervention characteristics
As demonstrated in Tables 1 and 2, all interventions in the included studies lasted for at least 1 week, with the longest one lasting for 10-18 weeks. 31The actual prehabilitation duration was assessed in three studies, 27,29,31 with a mean or median time range of 7.6-63 days.In four studies, 26,27,31,33 multimodal prehabilitation was implemented, with all studies including preoperative exercise, nutritional support, and psychological support.Halliday et al. 33 and Janssen et al. 26 adopted the same program, that is, the PREPARE program, whereas Dewberry et al. 31 adopted the STRENGTH program.Four RCTs from China [28][29][30]32 employed unimodal prehabilitation that is, nutrition-only prehabilitation. Incontrast, Liu et al. 32 additionally administered 30-day post-discharge home EN to the patients in the prehabilitation group.Except for one study, 31 which did not explicitly report the type of nutrition prehabilitation, ONS was the only choice of nutrition in five studies.[27][28][29][30]32 Furthermore, in addition to ONS, the PREPARE program 26,33 also allowed EN via jejunostomy.The exercise intervention primarily comprised a mixture of home-based, personalized aerobic, and strength or resistance exercises preoperatively 26,27,33 ; however, the Be Fit/Be Well exercise program was not well-defined.27,31,33 In seven studies, a negative control group was included.[26][27][28][29][30][31]33 However, Liu et al. 32 administered the same preoperative nutritional support as the trial group to patients in the control group, with a Nutrition Risk Screening 2002 (NRS2002) score of ≥3.

| Risk of bias
The Cochrane Collaboration's tool was used in five RCTs [27][28][29][30]32 (Figure S1a,b). Owng to the nature of the intervention, masking participants or healthcare professionals was impossible.As a result, a high risk of performance bias was observed.Wang et al. 30 and Zhao et al. 28 did not report concrete baseline statistics, resulting in significant underlying differences in the baseline; therefore, these studies exhibited high risk in terms of other biases.The reporting bias of most RCTs [28][29][30]32 was unclear because they did not provide the protocols to evaluate the predetermined outcomes, except for one 27 RCT that mentioned that the trial protocol was at low risk.NOS was used to assess the three cohort studies 26,31,33 (Figure S1c).One study 26 lost a star in comparability because control for the pTNM stage between the groups was not completed (p = 0.014).Another study 31 had a retrospective design and the outcomes of interest were present at the start of the study; therefore, it lost a star in selection.Publication bias was not evaluated because only eight studies were included (<10).
Any prehabilitation, that is, unimodal combined with multimodal prehabilitation, significantly decreased the risk of any postoperative complication by 23% (95% CI = 0.66-0.90),with little heterogeneity (I 2 = 0%, p = 0.97; Figure 2).This effect was consistent and not affected by the study design.Both RCTs and non-RCTs suggested that prehabilitation can effectively mitigate any postoperative complication (Figure 2D).Furthermore, the outcomes where only multimodal prehabilitation studies were analyzed were similar to the overall pooling result (RR = 0.78, 95% CI = 0.66-0.93; Figure 2A).However, the results were not statistically significant (RR = 0.74, 95% CI = 0.54-1.01; Figure 2A) in studies on unimodal (only nutrition) prehabilitation.Stratification by whether the ERAS program was applied in perioperative patient care revealed a significant decrease in any postoperative complication favoring prehabilitation (RR = 0.78, 95% CI = 0.67-0.92)under the ERAS settings (Figure 2B).Prehabilitation significantly decreased the risk of any postoperative complication in patients with EC and GC (Figure 2C).

| Hospital readmission
The hospital readmission rate was reported in six studies 26,27,29,[31][32][33] (Table 3 and Figure 5).However, two studies 27,32 did not provide a clear timescale, whereas others reported the rate within 30 26,29,31,33 or 90 days 31 after discharge.In these six studies, the total readmission rate (within 30 days or without explicit time) was 9.2% (20/218) and 7.9% (14/177) in the prehabilitation and control groups, respectively.Then, hospital readmission was stratified by multimodal or unimodal prehabilitation.The overall pooled outcomes and subgroup analysis results suggested statistical insignificance for the effect of any prehabilitation on hospital readmission (Figure 5).

| Mortality
Mortality within 30 days 31,32 or 90 days 26,31,32 after discharge or in the hospital 27 was reported in four studies. 26,27,31,32Owing to heterogeneity (different cutoff points for time) and low incidence (Table 3), a meta-analysis of the effect of any prehabilitation on mortality could not be conducted.However, none of these studies conducted follow-up and measured long-term mortality.

| DISCUSSION
Owing to their distinct characteristics, the pooled outcomes were stratified based on unimodal (nutrition-only) and multimodal prehabilitation.Prehabilitation, where nutritional intervention was needed but the number of preoperative interventions was not restricted, could significantly decrease the risk of any postoperative complication, a primary complication of interest, by 23% after esophagectomy and gastrectomy.When stratified, multimodal prehabilitation generated a similar result; however, the results of unimodal prehabilitation were no longer statistically significant.Presumably, multimodal prehabilitation is superior to unimodal prehabilitation in terms of decreasing any postoperative complication.
After esophagectomy and gastrectomy, postoperative pulmonary complications such as atelectasis, chylothorax, and pneumonia; severe complications (CDC grade 3 or higher); and anastomotic leakage were prevalent in patients with cancer, imposing adverse effects on the short-and long-term outcomes, including morbidity and mortality; preventing such complications may improve overall survival. 3,4,35Therefore, we also analyzed these three types of postoperative complications.The outcomes indicated that prehabilitation decreases the risk of postoperative severe and pulmonary complications but not that of anastomotic leakage.Among them, multimodal prehabilitation may be superior to unimodal prehabilitation in decreasing severe and pulmonary complications; however, this finding should be further confirmed because only two RCTs 29,32 (n = 116) in the unimodal prehabilitation subgroup reported outcomes of a part of these complications.In this meta-analysis, we discovered the benefits of prehabilitation that included nutritional interventions to decrease the incidence of any postoperative complication, including some common or severe complications, in patients with esophagogastric cancer.Among them, multimodal prehabilitation may confer more advantages than unimodal prehabilitation.A decrease in postoperative complications positively affects the quality of life, hospital days and costs, and overall survival of patients. 36 all clinical settings, the estimated effect of prehabilitation on LOS was small (mostly decreased by <1 day).Although LOS decreased, the extent of such a reduction is not extremely meaningful in clinical settings.Furthermore, such an outcome appears to contradict the significant decrease in any postoperative complication, which markedly prolongs LOS. 37We hypothesized the following reasons for this: (a) an enhanced recovery protocol program 2.0 planned the discharge day at 6 for patients after esophagectomy without or with minor complications (the shortest LOS to the best of our knowledge; in practice, the median discharge day was seven in this study). 6ecause most of the included studies (3/5) followed the ERAS protocol in both groups, the mean LOS in the intervention and control groups was already remarkably similar to this idealized limit (6 days).Using any other intervention to further decrease LOS will be challenging.(b) Most of the included studies (4/5) expressed LOS using median and interquartile range; however, they were converted to mean and SD for statistical analysis.Some of these raw data may be skewed, and such conversions can distort the true effect.In the present study, we could only reveal that prehabilitation exerts a limited effect on decreasing the LOS of patients with esophagogastric cancer who had undergone surgery.
Preoperative nutritional support is a vital component of prehabilitation.In the included studies, ONS was predominantly administered to provide preoperative nutritional support because it is more convenient, less invasive, and has fewer complications associated with tube placement compared with EN or parenteral nutrition in patients without GI obstruction.However, special and repeated incentives are warranted because compliance with ONS intake is frequently limited. 38In patients with GI obstruction, either EN or parenteral nutrition can accelerate postoperative recovery. 39Because no specific evidencebased recommendations are available, the target settings for energy and protein intake were markedly different in the included studies.We did not include studies that examined preoperative immunonutrition (e.g., arginine, ω-3 fatty acids, nucleotides, and glutamine) because these agents are primarily utilized to improve host immune status and inflammatory responses 40 ; this is inconsistent with the objective of our study.The implementation of preoperative nutritional interventions is based on three primary considerations: (a) to improve the nutritional status of the body in advance (focus on prevention) to optimally cope with the high catabolic state during and after surgery, inadequate nutrition intake resulting from postoperative fasting, and body depletion owing to possible postoperative complications, and not necessarily to replace nutritional deficits. 13,41Nutritional interventions conducted some amount of time in advance, rather than waiting until the development of malnutrition, that is, a forward movement of the intervention gateway, is considered an excellent protocol in clinical settings. 42A superiority RCT to compare prehabilitation (nutrition and exercise) with rehabilitation (immediately after surgery) in patients undergoing colorectal resection for cancer revealed that prehabilitation can significantly improve the functional exercise capacity both preoperatively and postoperatively compared with rehabilitation. 43(b) The use of postoperative EN preparations often increases the incidence of nutrition-associated complications, including vomiting, abdominal distention, and ventilator-associated pneumonia. 44We hypothesize that preoperative ONS or EN facilitates a preadaptation process in the digestive tract to decrease the incidence of postoperative nutritionassociated adverse effects and provides a faster transition from parenteral nutrition to EN, as well as the adequate use of established EN preparations after surgery, accelerating body recovery 45 and allowing more nutrition intake, thereby establishing a positive cycle.(c) Preoperative exercise alone without nutritional supplementation may limit exercise intensity and duration, making it less effective.A study revealed that patients who did not achieve their preoperative exercise goals tended to exhibit an increased need for nutritional interventions at baseline. 46lthough nutrition is essential, exercise can also play a vital role in promoting protein synthesis by muscles. 41he rational arrangement of exercise and nutritional supplementation preoperatively can increase the benefits of both measures for patients; for example, ingesting carbohydrates 3-4 h before exercise can increase liver and muscle glycogen reserves and improve the performance of endurance exercise. 47Hypertrophy in skeletal muscle in response to resistance exercise requires the early ingestion of an oral protein supplement after resistance training. 48n the currently included studies, nutrition and exercise were two independent interventions, and further exploring how they can be combined and interspersed more rationally and efficiently is worthwhile.
In this meta-analysis, there were differences in the duration of prehabilitation interventions in the included studies, with a range of 1 to 10-18 weeks; this may have affected the interpretation of the results.In previous meta-analyses of unimodal or multimodal prehabilitation for abdominal cancer surgery, similar variations in the duration of prehabilitation interventions have been observed, with a range of 2-14 weeks. 49,50Subgroup analyses suggested that prehabilitation for more than 3 weeks decreased the overall complication rate compared with a shorter intervention time. 49However, the risk of cancer progression associated with a longer preoperative waiting time should be carefully considered.Because only three studies 27,29,31 in our meta-analysis revealed the actual duration of prehabilitation interventions, subgroup analysis was not performed based on intervention duration.
Only one study 27 in this meta-analysis evaluated the effect of prehabilitation on the changes in the functional capacity of patients and confirmed the improved functional capacity of the patients in the prehabilitation group both before and after surgery (absolute change in 6-min walk distance, a primary indicator in the 6-min walk test to determine the functional capacity 51 ).If an intervention to preserve functional capacity is not rapidly implemented in catabolic patients, functional deterioration will occur. 52he improvement in the physical function owing to prehabilitation can improve compliance and allow patients with esophagogastric cancer to better complete their planned treatment. 27o the best of our knowledge, this is the first systematic review and meta-analysis to investigate prehabilitation, thereby emphasizing the effectiveness of nutrition and multimodality, in patients with UGI cancer undergoing surgery.Minnella et al. 27 were the first to conduct a pragmatic RCT of a structured preoperative conditioning intervention involving nutrition and exercise prehabilitation for patients with UGI cancer completed in 2017.One meta-analysis on prehabilitation for colorectal surgery revealed shortened LOS (~2 days), earlier functional recovery postoperatively, and decreased postoperative complications. 19This is consistent with the conclusions drawn in this meta-analysis, suggesting that prehabilitation positively affects the postoperative outcomes of total GI.A recent systematic review of prehabilitation for patients undergoing UGI surgery summarized the effect of different prehabilitation interventions (including single intervention or various combinations of nutritional, exercise, and psychosocial interventions) on patient biopsychosocial and service outcomes, finding that prehabilitation improved preoperative impairments and that multimodal prehabilitation appeared to achieve better outcomes. 53In the studies included in our meta-analysis, nutrition-based prehabilitation was also found to improve functional capacity 27 or reduce weight loss 31 in the preoperative period, but was not quantitatively synthesized due to the paucity of studies reporting preoperative outcomes and the variability of outcome metrics.Future studies could focus more on preoperative outcomes along with postoperative outcomes.
Our review has several limitations.First, the sample size was small (n = 661) and all studies did not report all the results of interest.Therefore, the results of subgroup analyses should be cautiously interpreted.Second, similar to other meta-analyses, inevitable differences were observed in baseline data, concept definitions, and study designs across the included studies.Where possible, we assessed and decreased these differences using more stringent inclusion and exclusion criteria, statistical tests, and subgroup analyses.In one RCT, 32 ONS was prescribed as a preoperative treatment regimen in the control group if the NRS2002 score was ≥3, potentially underestimating the effect of the intervention group.Because the high heterogeneity could not be decreased, we only qualitatively described postoperative mortality.Third, owing to the limited number of studies completed to date, we could not definitively judge which unimodal and multimodal prehabilitation was superior and what was the best intervention duration.Fourth, blinding patients and healthcare providers was challenging; therefore, a high performance bias was observed in RCTs and the effect of the interventions may have been overestimated.
Based on the findings of this review, we propose recommendations for future studies on prehabilitation.First, specific patient classifications, including the elderly or those with preoperative malnutrition or sarcopenia, should be further investigated to identify who benefits the most.Second, multimodal prehabilitation may decrease patient compliance owing to more cumbersome interventions in the multimodal setting; therefore, the advantages of multimodal over unimodal prehabilitation should be explored by considering patient compliance and the requirement of appropriate interventions such as the sequential combination of exercise and nutrition. 47,48Furthermore, better monitoring and reporting of patient adherence are essential. 54Third, including patient-oriented results such as nutrition-associated complications and functional capacity, a major determinant of surgical prognosis, 55 is vital.Furthermore, exploring the changes in body components is encouraged.Fourth, uniform definitions should be adopted for reporting complications, including the Esophagectomy Complications Consensus Group definition. 56,57Fifth, prehabilitation is a relatively new approach in UGI surgery.Furthermore, results have not been published for 13 prehabilitation research protocols associated with esophagogastric cancer surgery (Figure 1).Therefore, an update of this metaanalysis is expected.

| CONCLUSIONS
Nutrition-based prehabilitation, with nutrition as a vital component, can significantly decrease any postoperative complication, including severe and pulmonary complications, in patients with esophagogastric cancer undergoing surgery.Furthermore, multimodal prehabilitation may be more advantageous than unimodal prehabilitation in decreasing postoperative complications.However, prehabilitation to decrease LOS was not clinically significant because a significant reduction was not observed (0.77 days).Additional RCTs and an updated meta-analysis are warranted in the future to acquire more convincing evidence.

F I G U R E 1
Preferred Reporting Items for Systematic Reviews and Meta-Analyses flow diagram of study selection.
Abbreviations: C, control; CDC, Clavien-Dindo classification; I, intervention; IQR, interquartile range; NA, not available; SD, standard deviation.a Including symptoms of feeding intolerance and other non-feeding related complication.b CDC III and higher.

F I G U R E 2
Effects of any prehabilitation on any postoperative complication in patients with esophagogastric cancer after esophagectomy and gastrectomy (A) stratified by multimodal and unimodal (only nutrition) prehabilitation; (B) in an ERAS and traditional care setting; (C) with cancer excluding GC and cancer including GC; and (D) in RCTs and non-RCTs.CI, confidence interval; ERAS, enhanced recovery after surgery; GC, gastric cancer; RCT, randomized controlled trial.F I G U R E 3 Effect of multimodal and unimodal (only nutrition) prehabilitation on (A) severe postoperative complications; (B) postoperative pulmonary complications; and (C) postoperative anastomotic leakage in patients with esophagogastric cancer after esophagectomy and gastrectomy.CI, confidence interval.

F I G U R E 4 F I G U R E 5 | 15 of 20 SHEN
Effect of any prehabilitation on LOS in patients with esophagogastric cancer after esophagectomy and gastrectomy (A) stratified by multimodal and unimodal (only nutrition) prehabilitation; (B) in an ERAS and traditional care setting; (C) with cancer excluding GC and cancer including GC; and (D) in RCTs and non-RCTs.LOS, length of hospital stay; CI, confidence interval; ERAS, enhanced recovery after surgery; GC, gastric cancer; RCT, randomized controlled trial.Effect of multimodal and unimodal (only nutrition) prehabilitation on hospital readmission in patients with esophagogastric cancer after esophagectomy and gastrectomy.CI, confidence interval.et al.
T A B L E 33a Starting oral feeding on postoperative day one after a minimally invasive Ivor-Lewis esophagectomy.bThisstudyfollowedPREPAREprehabilitationprogramme,firstlyintroduced at St Mary's Hospital, London(Halliday,33).When certain details were not specifically described, they were considered to be the same as Halliday et al.33  cMissing data for two patients (both in the prehabilitation group) who did not have surgery.neoadjuvantchemotherapy;NCRT:neoadjuvantchemoradiotherapy; NRS2002, nutrition risk screening 2002; NS, not specific; ONS, oral nutritional supplement; SD, standard deviation.aCaculatedasthevolume of exercise completed by the patient each week in MET minutes/week divided by the prescribed volume of exercise each week in MET minutes/week.bThisstudyfollowedPREPARE prehabilitation programme, firstly introduced at St Mary's Hospital, London (L.J.Halliday, 2021).When certain details were not specifically described, they were considered to be the same as Halliday et al.33  cIntegrating both exercise (number of weekly training sessions completed) and nutrition (adherence to the prescribed protein supplementation).